Slimming composition for topical treatment, containing two types of liposomes, and use thereof

ABSTRACT

Compositions containing a first dispersion of lipid vesicles which are capable of penetrating into the deep layers of the skin and which contain at least one active agent chosen from lipolytic agents, draining agents and firming agents, for treating these deep layers, and a second dispersion of lipid vesicles which are capable of penetrating into the surface layers of the skin and which contain at least one active agent chosen from cutaneous surface treatment agents, exfoliation agents, smoothing agents and softening agents for the skin, for treating these surface layers, are effective as slimming agents for combating plumpness.

This is a Division, of application Ser. No. 08/367,421 filed on Dec. 30,1994 now U.S. Pat. No. 5,637,316.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to compositions useful for decreasingand/or combating plumpness and/or excess weight for the purpose ofobtaining a generalized or localized cosmetic and/or therapeuticslimming effect on the human or animal body. The present invention alsorelates to a method for slimming the body, by applying such acomposition topically.

2. Discussion of the Background

Plumpness and/or excess weight is associated with the dysfunction ofcertain cells, known as adipocytes, which contain variable amounts offats in the form of triglycerides which are themselves synthesized, invivo by the adipocytes, enzymatically (lipogenesis) from free fattyacids and glucose contained in the body and supplied thereto via certainfoods. In parallel with this, the triglycerides formed and then storedmay be re-degraded, also via an enzymatic route (lipolysis), into fattyacids, glycerol and/or glycerol esters.

If, for various reasons, (poor hormonal functioning, excessively richdiet, inactivity, ageing), an appreciable imbalance develops in the bodybetween lipogenesis and lipolysis in favor of lipogenesis, anaccumulation of triglycerides occurs in the adipocytes, which may resultin excess weight, possibly leading to obesity.

Although this excess weight was hitherto well tolerated, it nowadaysconstitutes, and especially in women, an ever-increasing problem bothphysical and aesthetic, or even psychological.

Several slimming methods have already been proposed for the purpose ofcombating excess weight, such as strict diets which as soon as they arestopped, very rapidly result in a new excess of weight which is oftengreater than that which was the cause of these diets, or alternativelysurgical methods such as liposuction, these methods often beingexpensive and intricate.

The need thus exists for a "gentle" method, that is to say one which isnot surgical or strict, for treating and/or preventing excess weight.

Many examples are known of cosmetic or dermatological compositionsintended for treating the skin, which have one or more active agentsthat are suitable for treating the skin and which are encapsulated inlipid spherules or vesicles (also known as liposomes).

Lipid spherules or vesicles are understood to refer to particles formedof a membrane consisting of one or more concentric lamellae, theselamellae containing one or more bimolecular layers of amphiphilic lipidsencapsulating an aqueous phase. The aqueous phase may containwater-soluble active substances and the bimolecular layers ofamphiphilic lipids may contain lipophilic active substances.

These spherules generally have a mean diameter of between 10 nm and 5000nm. Among the many documents published regarding this matter, there maybe mentioned the French Certificate of Addition 2,408,387 whichdescribes a composition based on aqueous dispersions of ionic ornonionic lipid spherules encapsulating at least one active substance.More precisely, this document describes compositions containing at leasttwo dispersions of spherules containing different active agents, for thepurpose of obtaining a mixed system, that is to say a system in which afirst dispersion of spherules containing a first type of activesubstance is combined with a second dispersion of spherules containinganother type of active substance, which enables the two types ofsubstances to act simultaneously at the time of treatment and possiblyto obtain a synergistic effect which would not be produced if these twotypes of substances were made to act successively and separately.

It is well known that the skin consists of surface layers, the stratumcorneum, and of deep layers, the live epidermis and the dermis. However,specific delivery of such an active agent into the surface layers and,simultaneously, of the same or another active agent into the deeplayers, is not known from the prior art.

Thus, there remains a need for a gentle method of combating plumpness.There also remains a need for compositions useful in such a method.

SUMMARY OF THE INVENTION

Accordingly, it is one object of the present invention to provide anovel method for combating plumpness.

It is another object of the present invention to provide a gentle methodfor combating plumpness.

It is another object of the present invention to provide novelcompositions which are useful in such methods.

These and other objects which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat compositions comprising a first dispersion of lipid vesicles whichare capable of penetrating into the deep layers of the skin and whichcontain at least one active agent chosen from lipolytic agents, drainingagents and firming agents, for treating these deep layers, and a seconddispersion of lipid vesicles which are capable of penetrating into thesurface layers of the skin and which contain at least one active agentchosen from cutaneous surface treatment agents, exfoliation agents,smoothing agents and softening agents for the skin, for treating thesesurface layers, are effective slimming agents useful for combatingplumpness and simultaneously treating the surface layers and deep layersof the skin.

The invention relates, therefore, to a slimming composition and to acosmetic treatment process which fulfil this need. More particularly,this slimming composition comprises at least one active agent which isconveyed via at least two distinct types of lipid vesicles.

Thus, the inventors have now developed cosmetic slimming compositions,which allow the simultaneous action of two different active agents, andwhich furthermore allow these active agents to act in different areas ofthe skin, that is to say in the surface layers and in the deep layers ofthe skin, thereby very markedly enhancing the effectiveness of thesecompositions and the complementary or synergistic effect of the slimmingactive agents used.

The inventors have also developed cosmetic slimming compositions, whichenable the same active agent to act simultaneously in the surface layersand in the deep layers of the skin, providing a more complete andtherefore a more effective treatment against excess weight.

According to a specific embodiment, the active agents contained in thefirst dispersion of vesicles and in the second are the same.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The Applicant has used a means of classifying vesicles which enables aperson skilled in the art readily to select lipid vesicles capable ofconveying the active agent to the deep layers of the skin, known asvesicles with deep-down action, and those capable of conveying theactive agent to the surface layers of the skin, known as vesicles actingat the surface.

This classification is made on the basis of the diffusion constant D ofa probe introduced into the vesicles. This probe isN-(1-oxyl-2,2,6,6-tetramethyl-4-piperidyl)-N,N-dimethyl-N-hydroxyethylammoniumiodide, ASL, of formula (I): ##STR1##

Vesicles for which the diffusion constant D of the probe into thestratum corneum is>1×10⁻⁷ cm² S⁻¹ are vesicles which are capable ofpenetrating into the deep layers of the skin.

Vesicles for which the diffusion constant D of the probe into thestratum corneum is<1×10⁻⁷ cm² s⁻¹ are vesicles which are capable ofconveying the active agent to the surface layers of the skin.

The vesicles of the first type, the so-called vesicles with deep-downaction, are generally in the fluid state at room temperature (about 20°C.), and those of the second type, the so-called vesicles acting at thesurface, are generally in the gelled state at room temperature. Themeans of recognizing the state of the vesicles consists in determiningthe phase (fluid-gel lamellar) transition temperature of the main lipidconstituting the membrane thereof, by differential thermal analysis(DTA).

Other characteristics of these vesicles relate to their ability todeliver the active agent to a greater or lesser depth in the skin. Thisis particularly the case for the degree of encapsulation.

Glucose is a labelling agent conventionally used for this type ofdetermination (see in particular, Liposomes a practical approach by R.R. C. New, IRL Press, pp. 125-136 (1990)).

The degree of encapsulation is expressed as the volume of glucosesolution encapsulated in the vesicles, measured in μl relative to theunit weight (mg) of the lipids constituting the membrane. This degree ofencapsulation is determined immediately after the step of separation ofthe free glucose from the encapsulated glucose (T₀), as well astwenty-four hours after this separation (T₂₄ hours)

The difference between these two successive determinations illustratesthe permeability of the vesicles with respect to the encapsulatedglucose, which may also be referred to as their encapsulation potential.

The first category of vesicles (delivering the active agent into thedeep layers of the skin) has a high encapsulation potential for thesmall water-soluble molecules which are conventionally modelled byglucose, this encapsulation potential being maintained for at least 24hours. The second category of vesicles (delivering the active agent intothe surface layers of the skin) does not retain glucose in theencapsulated state for the same amount of time.

The main lipids constituting the vesicles of the first type (deepdelivery of the active agent) are composed of at least one linear andsaturated fatty chain of length ranging from 16 to 30 carbon atoms, suchas hydrogenated phospholipids (from plants or from egg), saturatedsynthetic phospholipids such as dipalmitoylphosphatidylcholine, andpolyol alkyl ethers or polyol alkyl esters containing one, two or threefatty chains per molecule. These lipids are used alone or as a mixture.

The main lipids constituting the vesicles of the second type (activeagent delivered at the surface) are chosen in particular from the groupcomprising ionic lipids, especially such as natural plant- or egg-basedphospholipids, containing unsaturated fatty chains having from 16 to 30carbon atoms; nonionic lipids such as polyol alkyl ethers or polyolalkyl esters containing one or more fatty chains per molecule, includingat least one fatty chain with a length of less than 16 carbon atoms,such as lauryl polyglyceryl-6-cetearyl glycol ether, described in detailin French Patent Application FR 92-09603 filed by L'Oreal, and mixturesthereof.

It is possible, in a known manner, to incorporate into the lipid phaseconstituting the lipid membrane of the vesicles, at least one additivechosen from the group formed of sterols (phytosterols, cholesterol orpolyoxyethylenated phytosterols); long-chain alcohols, diols and triols(phytanetriol), long-chain amines and the quaternary ammoniumderivatives thereof; phosphoric esters of fatty alcohols and the alkalimetal (Na or K) salts thereof, such as dicetyl phosphate, sodium dicetylphosphate, alkyl sulfates (sodium cetyl sulfate), alkali metal salts ofcholesterol sulfate or of cholesterol phosphate, the sodium salt ofphosphatidic acid, and lipoamino acids and the salts thereof, such asthe sodium acylglutamates.

Examples of vesicles of the first type (delivering the active agent intothe deep layers of the skin) which may be mentioned are vesiclesobtained from the following lipids (CTFA name):

A/cholesterol/casein lipoamino acid, especially in a 45/45/10 weightratio (where A is a triglyceryl cetyl ether marketed by the companyChimex under the name Chimexane NL);

B/cholesterol/dicetyl phosphate, especially in a 60/35/5 weight ratio(where B is a mixture of triglyceryl mono-, di-and tricetyl ether,marketed by the company Chimex under the name Chimexane NT);

Span 40 (from ICI, or Sorbitan palmitate)/cholesterol/sodiumacylglutamate (sold under the name HS11 by the company Ajinomoto),especially in a 47.5/47.5/5 weight ratio;

PEG 8 stearate/cholesterol/sodium acylglutamate, especially with a47.5/47.5/5 weight ratio (where PEG 8 stearate is polyethylene glycolcontaining 8 units of ethylene oxide, marketed by the company Unichemaunder the name PEG 400 stearate);

PEG 8 stearate/cholesterol/phytanetriol/sodium acylglutamate, especiallywith a 47.5/20/27.5/5 weight ratio;

Hydrogenated lecithin/polyoxyethylenated phytosterol containing 5 unitsof ethylene oxide, especially in a 60/40 weight ratio;

Polyoxyethylenated methylglucose distearate containing 20 units ofethylene oxide/cholesterol/sodium acylglutamate, especially in a45/45/10 weight ratio (the distearate being, for example, that soldunder the name Glucam E 20 distearate by Amerchol);

A/cholesterol/dicetyl phosphate, especially with a 47.5/47.5/5 weightratio;

Diglyceryl distearate (for example that sold by Nihon under the nameEmalex DS G2)/cholesterol/sodium acylglutamate, in a 45/45/10 weightratio;

Sucrose mono- and distearate (for example that sold by Grillo under thename Grilloten PSE 141 G)/cholesterol/sodium acylglutamate, especiallyin a 45/45/10 weight ratio;

Tetraglyceryl tristearate (for example that sold by Nikkol under thename Tetraglyn 3S)/cholesterol/sodium acylglutamate, especially in a45/45/10 weight ratio.

Examples of vesicles of the second type (delivering the active agentinto the surface layers of the skin) which may be mentioned are vesiclesobtained from the following lipids:

Sunflower lecithin;

Natipide II (soya lecithin/ethanol/water in a 20/16/64 weight ratio,marketed by Nattermann);

C (soya lecithin/cholesterol/propylene glycol in a 60/20/20 weightratio, marketed by Nattermann under the name NAT 50 PG);

D/dimyristyl phosphate, especially in a 95/5 weight ratio (where D is alauryl polyglyceryl-6-cetearyl glycol ether marketed by the companyChimex under the name Chimexane NS).

Table I below gives, for some of the vesicles obtained using the abovelipids, the diffusion constant D for ASL in the stratum corneum and inthe epidermis/dermis, as well as the degree of encapsulation of glucoseand the phase transition temperature of the main lipid constituting themembrane. The diffusion constant was measured for an encapsulated ASLconcentration of 0.35% by weight based on the total weight of thecomposition.

                                      TABLE I                                     __________________________________________________________________________                          Diffusion                                                                     coefficient                                                                             Degree of                                                           D in 10.sup.-7 cm.sup.2 s.sup.-1                                                        encapsulation                                                                        Phase                                                Proportions                                                                           in the                                                                             in the                                                                             of glucose in                                                                        transition                                           % by weight                                                                           stratum                                                                            epidermis/                                                                         μl/mg                                                                             temperature                            Ref.                                                                             LIPID SYSTEMS                                                                            (mg)    corneum                                                                            dermis                                                                             T.sub.o                                                                           T.sub.24h                                                                        in °C.                          __________________________________________________________________________       1st type - deep down                                                       1  A/cholesterol/casein                                                                     45/45/10                                                                              42   5    7.5 6.8                                                                              50                                        lipoamino acid                                                                           (67.5/67.5/15)                                                  2  B/cholesterol/dicetyl                                                                    60/35/5 58   2    11.1                                                                              11.1                                                                             54                                        phosphate  (90/52.5/7.5)                                                   3  Span 40/cholesterol/                                                                     47.5/47.5/5                                                                           42   2    13.8                                                                              13.8                                                                             50                                        sodium acylglutamate                                                                     (71.25/71.25/7.5)                                               4  PEG 8 stearate/                                                                          47.5/47.5/5                                                                           42   2    14.4                                                                              14.4                                                                             55                                        cholesterol/sodium                                                                       (71.25/71.25/7.5)                                                  acylglutamate                                                              5  PEG 8 stearate/                                                                          47.5/20/27.5/5/5                                                                      8.3  2.5  4.1 3.0                                                                              55                                        cholesterol/phytanetriol/                                                                (71.25/30/                                                         sodium acylglutamate                                                                     41.25/7.5)                                                      6  Hydrogenated lecithin/                                                                   60/40   8    2    6.0 4.8                                                                              80                                        polyoxyethylenated                                                                       (90/60)                                                            phytosterol                                                                   2nd type - surface                                                         7  Sunflower lecithin                                                                       100     0.3  0.2  1.6 0  <0                                                   (150)                                                           8  Natipide II (soya                                                                        20/16/64                                                                              0.4  0.2  0.4 0  <0                                        lecithin/ethanol/water)                                                                  (30/24/96)                                                      9  C (soya lecithin/                                                                        60/20/20                                                                              0.25 0.1  1.8 0  <0                                        sterols/propylene glycol)                                                                (90/30/30)                                                      10 D/dimyristyl phosphate                                                                   95/5    0.3  0.2  2.0 0  14                                                   (142.5/7.5)                                                     __________________________________________________________________________

Measurement of the diffusion constant D is carried out by combining twomethods using a paramagnetic probe, ASL: one-dimensional and periodicelectron paramagnetic resonance (EPR), on the one hand, and EPR kineticimaging, on the other hand. These two methods are respectively describedin the articles "Evaluation of liposomes as drug carriers into the skinby one-dimensional EPR imaging" by V. Gabrijelcic et al., InternationalJournal of Pharmaceutics, vol. 62, pp. 75-79, Elsevier (1990), and"Liposome entrapped molecules penetration into the skin measured bynitroxide reduction kinetic imaging" by V. Gabrijelcic et al.,Periodicum Biologorum, vol. 93, No. 2, pp. 245-246 (1991).

Measurement of the degree of encapsulation is carried out as describedin the Liposomes a practical approach, by R. R. C. New, IRL Press, pp.125-136 (1990) cited above, and that of the phase transition temperatureis carried out as described above.

Advantageously, several active agents are used simultaneously in eachcategory of vesicles, these active agents having the same functionand/or imparting to the skin, at the surface and deep down, the sametype of effect; the agents active at the surface and the agents withdeep-down action are thus complementary.

The agents active at the surface and the active agents with deep-downaction which may be used in the invention are those that areconventionally used in the cosmetic and/or dermatological field. Theymay be present in an amount of from 0.02 to 10% by weight, preferably0.1 to 5% by weight, based on the total weight of the composition.

The active agents with deep-down action are, for example, chosen fromasiatic acid; caffeine; nicotinic acid derivatives, such as α-tocopherolnicotinate or hexyl nicotinate; silicon; carnitine; coenzyme Q; escin;ruscogenin; draining, firming, lipolytic or veinotropic plant extracts;anti-glucose-uptake active agents; α-2-blocker compounds capable ofblocking the α-2 receptors at the surface of adipocytes, such as ginkgobiloba.

As plant extracts which may be used in the invention, there may inparticular be mentioned ivy, seaweed, butcher's broom, common horsechestnut, arborvitae, arnica, wild pansy, clematis, cola, blackcurrant,tea and rosemary.

The agents active at the surface are chosen, for example, fromkeratolytic agents, such as 5-octanoylsalicylic acid; salicylic acid;α-hydroxy acids such as lactic acid, malic acid, glycolic acid ortartaric acid or α-hydroxy acids from fruit, such as citric acid; andmoisturizing agents.

As moisturizing agents which may be used in the invention, there may bementioned polyhydroxylated alcohols such as sorbitol, glycerine,hexanetriol, propylene glycol, hexylene glycol and polyethylene glycols;sugars and the derivatives thereof; starches and the derivativesthereof; D-panthenol; hyaluronic acid; monoethanolamine lactamide andmonoethanolamine acetamide; 2-pyrrolidone-5-carboxylic acid; as well asmixtures of these various active agents.

The compositions according to the invention may be provided in all thepharmaceutical forms normally used for topical application, such asaqueous gels, emulsions, lotions, ointments, sera and, moreparticularly, vesicle-dispersed oil droplets such as those described inFrench patents FR-A-2,485,921 and FR-A-2,490,504.

As is known, in addition to the vesicles, a vegetable oil, mineral oil,silicone-containing oil or synthetic oil which is dispersed in anaqueous phase, and also hydrophilic adjuvants such as gelling agents,antioxidants, preserving agents, opacifying agents, lipophilic adjuvantssuch as essential oils and fragrances, pigments and fillers, may befound in the compositions of the invention, as described in the aboveFrench patents. For example, polyethylene beads may be added to providea cleaning action (scrub). The dispersed oil may be present in an amountof from 2 to 40% by weight, preferably 5 to 20% by weight, based on thetotal weight of the composition, and the adjuvants may be present in atotal amount of from 0.1 to 10% by weight, preferably 1 to 5% by weight,based on the total weight of the composition.

The invention also relates to a use of the composition defined above andto a process for decreasing and/or combating plumpness and/or excessweight on the human body, involving applying this composition locally orover all of the skin of the body. The invention also relates to a use ofthis composition for the preparation of an ointment intended to decreaseand/or to combat plumpness and/or excess weight.

The vesicles of both the first and second types suitably comprise 1 to90% by weight, preferably 5 to 70% by weight, more preferably 5 to 20%by weight, of the total weight of the composition.

The relative amounts of the vesicles of the first and second types inthe present compositions are suitably:

10 to 90% by weight of the vesicles of the first type, and

90 to 10% by weight of the vesicles of the second type, preferably:

30 to 70% by weight of the vesicles of the first type, and

70 to 30% by weight of the vesicles of the second type,

based on the total weight of the vesicles of the first and second types.

Other features of the invention will become apparent in the course ofthe following description of exemplary embodiments which are given forillustration of the invention and are not intended to be limitingthereof.

EXAMPLES

In all of the Examples, the term "qs 100 g" means that that ingredientis added in a sufficient amount so that the sum of the amounts of all ofthe ingredients is 100 g.

A. Production of lipid vesicles containing ASL:

The constituent lipids of the wall of the vesicles are weighed anddissolved in 10 ml of methanol. The alcoholic solution is thentransferred into a 50-ml round-bottomed flask with a ground joint, whichis subsequently placed on a rotary evaporator such that the contents arethermostatted at a temperature of 30° C. The evaporation is continueduntil a dry film of lipids is deposited on the wall of the flask.

3 ml of an aqueous 0.01 molar solution of ASL are then added to theflask, which is subsequently shaken by hand for about 10 minute, eitherat room temperature (20° C.) for the vesicles of Table I of referenceNos. 7 to 10, or at a temperature of 50° C. for the vesicles ofreference Nos. 1 to 6 of Table I. The medium is then left to equilibrateat room temperature for 2 hours, after which the dispersion is placed ina dialysis bag and in contact with 500 ml of distilled water. Dialysistakes place overnight. The next day, the water is changed and thedialysis is continued for a further 4 hours.

A cotton thread 0.3 mm thick is then soaked in the vesicle dispersionand then placed in contact with a section of skin cut from a pig's earwhich has been freshly taken from an abattoir intended for food supply.

The ear sample taken is rinsed with water and cut into slices 1 mmthick, 5 mm wide and 10 mm long and then placed in a maintenance cell.Measurements of the diffusion of ASL into the skin are made in the 24hours following the taking of the skin sample.

B. Production of the cosmetic composition:

1. Production of vesicles of the first type (diffusing deep down).

The vesicles (with deep-down action) are prepared according to a commonmethod for co-fusion of the various membrane constituents chosen (seeTable I). Thus, the membrane constituent having the lowest melting pointT_(m) is melted. The other membrane constituents are added, and themixture is then homogenized with moderate stirring and is finallypartially hydrated, while maintaining the melting temperature T_(m)defined above.

An aqueous solution of at least one first active agent for the deep-downtreatment is added to the paste obtained. The mixture is stirred with aturbine for 1 hour and 30 minutes in order to hydrate fully, whilemaintaining the temperature T_(m). One or more other active agents forthe deep-down treatment are added to the reaction medium, homogenizationis carried out and the temperature of the medium is lowered to roomtemperature (20° C.).

2. Production of vesicles of the second type (diffusing at the surface).

An aqueous solution of one (or more) second active agent for the surfacetreatment is introduced, at room temperature (20° C.) and with simplestirring, into the chosen mixture of constituents which are to form themembrane of the vesicles acting at the surface (see Table I). Vesiclesacting at the surface encapsulating the second active agent acting atthe surface are thus obtained.

3. Production of the "double-liposome" composition.

The fatty phase (the oils) of the composition is added to the mediumcontaining the vesicles with deep-down action, and it is dispersed (atroom temperature) with stirring. The reaction medium obtained is thenmixed with that containing the vesicles acting at the surface. Theadjuvants, such as preserving agents, a gelling agent which may beneutralized if necessary with a base (triethanolamine or sodiumhydroxide), and fragrances, etc., are then optionally added.

The product obtained is in the form of a soft and smooth white creamwhich may be used in the cosmetic and/or dermatological field fortreating plumpness and/or excess weight on the human and possibly animalbody.

Specific examples of cosmetic compositions in accordance with theinvention are given below.

Example 1. Double-liposome slimming cream.

    ______________________________________                                        Preparation A: Liposomes with deep-down action:                               Triglyceryl cetyl ether  7.6 g                                                Cholesterol              7.6 g                                                Sodium acylglutamate     0.8 g                                                Asiatic acid (active agent)                                                                            0.2 g                                                Nipagine (preserving agent)                                                                            0.1 g                                                Demineralized water qs   100 g                                                Preparation B: Liposome active at the surface:                                Chimexane NS/dimyristyl phosphate in a                                                                 20.0 g                                               95/5 weight ratio                                                             Salicyclic acid (active agent)                                                                         2.0 g                                                Glycerine (active agent) 15.0 g                                               Nipagine (preserving agent)                                                                            0.2 g                                                Demineralized water qs   100 g                                                Double-lipsome composition:                                                   Preparation A            12.5 g                                               Preparation B            10.0 g                                               Oils (vegetable oils and silicone oils)                                                                8.6 g                                                Plant extracts           4.1 g                                                Preserving agents        0.7 g                                                Carboxyvinyl polymer (gelling agent)                                                                   0.9 g                                                Sodium hydroxide         1.8 g                                                Demineralized water qs   100 g                                                ______________________________________                                    

The cream obtained may be applied daily either locally or all over thebody in order to decrease, or even to eliminate, excess weight.

Example 2: Double-liposome slimming cream.

This cream differs from that of Example 1 in that 5-n-octanoylsalicylicacid is used as the agent active at the surface, instead of salicylicacid.

Example 3: Double-liposome slimming cream.

    ______________________________________                                        Preparation A: Lipsomes with deep-down action:                                PEG 8 stearate            7.6 g                                               Cholesterol               7.6 g                                               Sodium acylglutamate      0.8 g                                               Caffeine (active agent)   3.0 g                                               98% Triethanolamine (neutralizing agent)                                                                1.5 g                                               Salicylic acid            1.3 g                                               Methylparaben (preserving agent)                                                                        0.1 g                                               Demineralized water qs    100 g                                               Preparation B: Liposomes active at the surface:                               Chimexane NS              20.0 g                                              Glycerine (active agent)  15.0 g                                              5-n-Octanoylsalicylic acid (active agent)                                                               2.0 g                                               Methylparaben (preserving agent)                                                                        0.2 g                                               Demineralized water qs    100 g                                               Double-liposome composition:                                                  Preparation A             12.5 g                                              Preparation B             10.6 g                                              Oils (vegetable oils and silicone oils)                                                                 8.6 g                                               Carboxyvinyl polymer (gelling agent)                                                                    0.9 g                                               Sodium hydroxide          1.8 g                                               Preserving agents         0.5 g                                               Demineralized water qs    100 g                                               ______________________________________                                    

This application is based on French Patent Application 93-15866 filed onDec. 30, 1993, which is incorporated herein by reference in itsentirety.

Obviously, numerous modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that, within the scope of the appended claims, theinvention may be practiced otherwise than as specifically describedherein.

What is claimed as new and is desired to be secured by Letters Patent ofthe United States is:
 1. A method for slimming, comprising applying tothe skin of a subject in need thereof an effective amount of acomposition for the simultaneous treatment of the layers of the stratumcorneum and deep layers of the skin, comprising a dispersion mixtureof:(a) a first dispersion of lipid vesicles which are capable ofpenetrating into the deep layers of the skin and which contain at leastone active agent selected from the group consisting of lipolytic agents,draining agents and firming agents, for treating these deep layers; and(b) a second dispersion of lipid vesicles which are capable ofpenetrating into the layers of the stratum corneum of the skin and whichcontain at least one active agent selected from the group consisting ofcutaneous surface treatment agents, exfoliation agents, smoothing agentsand softening agents for the skin, for treating these layers of thestratum corneum, and wherein said vesicles of said first dispersionensure a distribution ofN-(1-oxyl-2,2,6,6-tetramethyl-4-piperidyl)-N-dimethyl-N-hydroxyethylammoniumiodide (ASL) in the stratum corneum>1×10⁻⁷ cm² /s and in that saidvesicles of said second dispersion ensure a distribution of ASL in thestratum corneum<1×10⁻⁷ cm² /s.
 2. The method of claim 1, wherein saidvesicles of said first dispersion are in a fluid state at roomtemperature and said vesicles of said second dispersion are in a gelledstate at room temperature.
 3. The method of claim 1, wherein saidvesicles of said first dispersion exhibit an encapsulation potential ofglucose for at least 24 hours, and said vesicles of said seconddispersion exhibit an encapsulation potential of glucose for less than24 hours.
 4. The method of claim 1, wherein said vesicles of said firstdispersion are formed of lipids having at least one linear and saturatedfatty chain having from 16 to 30 carbon atoms.
 5. The method of claim 1,wherein said vesicles of said first dispersion are formed of at leastone lipid selected from the group consisting of natural hydrogenatedphospholipids, saturated synthetic phospholipids, polyol alkyl ethershaving at least one linear fatty chain, polyol alkyl esters having atleast one fatty chain, and mixtures thereof.
 6. The method of claim 1,wherein said vesicles of said first dispersion are formed of lipidsselected from the group consisting of:triglyceryl cetyl ether,cholesterol, and casein lipoamino acid; mixtures of triglyceryl mono-,di- and tricetyl ether, cholesterol, and dicetyl phosphate; triglycerylcetyl ether, cholesterol, and dicetyl phosphate; sorbitan palmitate,cholesterol, and sodium acylglutamate; PEG 8 stearate, cholesterol, andsodium acylglutamate; diglyceryl distearate, cholesterol, and sodiumacylglutamate; sucrose mono- and distearate, cholesterol, and sodiumacylglutamate; PEG 8 stearate, cholesterol, phytanetriol, and sodiumacylglutamate; polyoxyethylenated methylglucose distearate containing 20mol of ethylene oxide, cholesterol, and sodium acylglutamate;hydrogenated lecithin, and polyoxyethylenated phytosterol; andtetraglyceryl tristearate, cholesterol, and sodium acylglutamate.
 7. Themethod of claim 1, wherein said vesicles of said second dispersion areformed of lipids selected from the group consisting of natural ionicphospholipids having unsaturated fatty chains having from 16 to 30carbon atoms, polyol alkyl ethers having at least one fatty chain permolecule, comprising at least one fatty chain with a length of less than16 carbon atoms, polyol alkyl esters having at least one fatty chain permolecule, comprising at least one fatty chain with a length of less than16 carbon atoms.
 8. The method of claim 1 wherein said vesicles of saidsecond dispersion are formed of at least one lipid selected from thegroup consisting of:sunflower lecithin; soya lecithin, ethanol, andwater; soya lecithin, cholesterol, and propylene glycol; and laurylpolyglyceryl-6-cetearyl glycol ether and dimyristyl phosphate.
 9. Themethod of claim 1, wherein said active agent of said first dispersionand said active agent of said second dispersion provide the samefunction, the same effect, or both.
 10. The method of claim 1, whereinsaid active agent of said first dispersion and said active agent of saidsecond dispersion are the same.
 11. The method of claim 1, wherein saidactive agent contained in said first dispersion is selected from thegroup consisting of asiatic acid, caffeine, nicotinates, silicon,carnitine, coenzyme Q, escin, ruscogenin, plant extracts,anti-glucose-uptake active agents, and α-2-blocker compounds.
 12. Themethod claim of 1, wherein said active agent contained in said seconddispersion is selected from the group consisting of 5-octanoylsalicylicacid, salicylic acid, α-hydroxy acids, and moisturizing agents.
 13. Themethod of claim 1, further comprising (c) an oily phase dispersed in anaqueous phase.
 14. The method of claim 1, further comprising (d) ahydrophilic or lipophilic adjuvant.